The objective of this research is to study certain new drugs or new drug/radiation protocols for their effectiveness in achieving hematopoietic cell ablation prior to transplantation therapy of leukemia. We propose to approach the problem in a leukemic mouse model for transplantation therapy which has been developed by our group. This model consists of a leukemia sensitive mouse strain in which the disease is induced by injection of leukemia virus, and which is used as the therapy recipient, and of a histocompatible leukemia resistant F1-hybrid used as the marrow donor. Testing of the effectiveness of the drug/radiation treatment for transplantation therapy and the reduction of leukemia recurrence will involve a stepwise screening process. The first step will be a direct evaluation of the treatment's ability to eliminate hematopoietic stem cells in normal and leukemic mice. This will be done by evaluation of the survival of endogeneous hematopoietic stem cells, transplantable stem cells after drug and radiation exposure of the whole animal. Those regimens found most effective will be screened for other toxic side-effects and then put to the critical test in a transplantation therapy situation using the mouse model. The transplanted leukemic mice will be observed for: long-term survival, leukemia recurrence, and death from other than leukemic causes. The goal is to achieve in the model minimal leukemia recurrence and toxic side-effects, and to provide a bank of basic information from which clinicians can later draw in designing new marrow ablation protocols for transplantation therapy of human leukemia.